Biomedical subjects
Publications and source records attributed to R J Douglas.
Previously published studies on the relationship between brown adipose tissue thermogenesis and sudden infant death were examined and evidence was collated to support the hypothesis that a decreased level of mitochondrial uncoupling protein (or thermogenin) from the brown fat in some brown fat depots may play a role in SIDS aetiology.
Explore the source record for details and available documents.
Fifteen Swiss-Webster mice (Mus musculus) and eight cotton rats (Sigmodon hispidus) were inoculated orally with Caryospora bigenetica oocysts. Feces from these animals were collected from 0 to 180 days postinoculation (DPI) and examined for endogenously-produced oocysts using Nomarski microscopy. Oocysts were recovered from mouse feces at 0, 1, 2, 3, 5, 7, 8, 10, and 14 DPI, and from cotton rat feces at 1, 2, and 9 DPI. The recovered oocysts were determined to be from the original inocula due to the presence of thick walls, polar granules, and Stieda and substieda bodies. All animals exhibited clinical signs at 8 DPI. Developmental stages of C. bigenetica were identified in various tissues of seven cotton rats found dead at 9, 10, 11, 12, and 13 DPI. Caryocysts were found in muzzle, tongue, footpad, scrotum, and rectum of mice and cotton rats at 30 DPI. Fecal samples collected from mice on 0, 8, 10, 12, 14, 16, and 18 DPI, and from cotton rats on 0, 9, 11, 13, 15, and 17 DPI were injected subcutaneously into 13 mice. Of the 13 mice, a Caryospora infection was observed only in the mouse inoculated with 0 DPI mouse feces. We propose that endogenously-produced C. bigenetica oocysts are not fecally-transmitted by Swiss-Webster mice or cotton rats.
Five pairs of female Swiss-Webster mice were caged with 5 males (2 females/1 male). Eight females were inoculated orally with 2.6 x 10(5) Caryospora bigenetica oocysts either 3 days before mating, 3 days after mating (PMD), 9 PMD, or 16 PMD. The remaining 2 females were inoculated orally with Hanks' balanced salt solution and served as controls. One female from each cage delivered naturally at full term and the second female delivered by cesarean section on postmating day 18. The number of offspring per litter ranged from 7 to 12. One female produced a litter of 3 stillborn and 5 liveborn offspring. Seven of 8 female mice exhibited swollen muzzles and footpads 8 days after inoculation. Caryospora bigenetica was identified in tissues of muzzle, tongue, footpad, uterus, and placenta at necropsy. This is the first report of C. bigenetica in uterus and placenta. Clinical signs and tissue infections were not observed in control mice or in any offspring of the 10 female mice. This study presents evidence that C. bigenetica is not transmitted transplacentally.
Two Hampshire-Landrace crossbred pigs were found to contain developmental stages of Caryospora bigenetica following oral inoculation with 1 x 10(8) oocysts. One pig was given intramuscular injections of methylprednisolone acetate. Both pigs displayed clinical signs of dermal coccidiosis from 3 to 10 days after inoculation, including swollen jowls and hocks, bilateral ocular discharges, generalized erythema, and lethargy. Meronts and gamonts were observed histologically in numerous tissues including jowl, ear, footpad, tongue, and lung at 10 days postinoculation. The present study is the first report of C. bigenetica infections in swine.
The standard one-dimensional Rall cable model assumes that the electrotonic structure of neurons does not change in response to synaptic input. This model is used in a great number of both theoretical and anatomical-physiological structure-function studies. In particular, the membrane time constant, tau m, the somatic input resistance, Rin, and the electrotonic length are used to characterize single cells. However, these studies do not take into account that neurons are embedded in a network of spontaneously active cells. Synapses from these cells will contribute significantly to the membrane conductance, especially if recent evidence of very high specific membrane resistance, Rm = 100 k omega.cm2, is taken into account. We numerically simulated the electrical behavior of an anatomically reconstructed layer V cortical pyramidal cell receiving input from 4000 excitatory and 1000 inhibitory cells firing spontaneously at 0-7 Hz. We found that, over this range of synaptic background activity, tau m and Rin change by a factor of 10 (80-7 msec, 110-14 M omega) and the electrotonic length of the cell changes by a factor of 3. We show that this significantly changes the response of the cell to temporal desynchronized versus temporal synchronized synaptic input distributed throughout the neuron. Thus, the global activity of the network can control how individual cells perform spatial and temporal integration.
The single neurone has been the guiding light for generations of neuroscientists. Now there are signs from experimental and theoretical work on the neocortex that we are on the threshold of a revolution in which the hegemony of the single neurone will be replaced by much more circuit-oriented concepts. We consider here why traditional views of the significance of single neurones are fading in power, and consider the problem of deciding on the form of a new order.
1. Extracellular and intracellular recordings were made from neurones in the visual cortex of the cat in order to compare the subthreshold membrane potentials, reflecting the input to the neurone, with the output from the neurone seen as action potentials. 2. Moving bars and edges, generated under computer control, were used to stimulate the neurones. The membrane potential was digitized and averaged for a number of trials after stripping the action potentials. Comparison of extracellular and intracellular discharge patterns indicated that the intracellular impalement did not alter the neurones' properties. Input resistance of the neurone altered little during stable intracellular recordings (30 min-2 h 50 min). 3. Intracellular recordings showed two distinct patterns of membrane potential changes during optimal visual stimulation. The patterns corresponded closely to the division of S-type (simple) and C-type (complex) receptive fields. Simple cells had a complex pattern of membrane potential fluctuations, involving depolarizations alternating with hyperpolarizations. Complex cells had a simple single sustained plateau of depolarization that was often followed but not preceded by a hyperpolarization. In both simple and complex cells the depolarizations led to action potential discharges. The hyperpolarizations were associated with inhibition of action potential discharge. 4. Stimulating simple cells with non-optimal directions of motion produced little or no hyperpolarization of the membrane in most cases, despite a lack of action potential output. Directional complex cells always produced a single plateau of depolarization leading to action potential discharge in both the optimal and non-optimal directions of motion. The directionality could not be predicted on the basis of the position of the hyperpolarizing inhibitory potentials found in the optimal direction. 5. Stimulation of simple cells with non-optimal orientations occasionally produced slight hyperpolarizations and inhibition of action potential discharge. Complex cells, which had broader orientation tuning than simple cells, could show marked hyperpolarization for non-optimal orientations, but this was not generally the case. 6. The data do not support models of directionality and orientation that rely solely on strong inhibitory mechanisms to produce stimulus selectivity.
1. Neurones from layers 2-6 of the cat primary visual cortex were studied using extracellular and intracellular recordings made in vivo. The aim was to identify inhibitory events and determine whether they were associated with small or large (shunting) changes in the input conductance of the neurones. 2. Visual stimulation of subfields of simple receptive fields produced depolarizing or hyperpolarizing potentials that were associated with increased or decreased firing rates respectively. Hyperpolarizing potentials were small, 5 mV or less. In the same neurones, brief electrical stimulation of cortical afferents produced a characteristic sequence of a brief depolarization followed by a long-lasting (200-400 ms) hyperpolarization. 3. During the response to a stationary flashed bar, the synaptic activation increased the input conductance of the neurone by about 5-20%. Conductance changes of similar magnitude were obtained by electrically stimulating the neurone. Neurones stimulated with non-optimal orientations or directions of motion showed little change in input conductance. 4. These data indicate that while visually or electrically induced inhibition can be readily demonstrated in visual cortex, the inhibition is not associated with large sustained conductance changes. Thus a shunting or multiplicative inhibitory mechanism is not the principal mechanism of inhibition.
1. We used anatomical methods to examine whether the geniculocortical afferent input to dendritic spines could be gated or 'vetoed' by an inhibitory input to the same spine. 2. Physiologically identified X- and Y-type afferents were injected intra-axonally with horseradish peroxidase (HRP), processed, and drawn under the light microscope. Selected regions of the terminal arbors were then serially sectioned for examination under the electron microscope. 3. Three-dimensional reconstructions of thirty-nine HRP-filled terminal boutons forming fifty asymmetric (type 1) synapses showed that thirty-one synapses were on the heads of dendritic spines. Only two of thirty-one spine heads received an additional symmetric (type 2) synapse, which is presumed to be inhibitory. 4. Examination of twenty-three boutons from two clutch cells (a GABA (gamma-aminobutyric acid)-ergic smooth cell) that form symmetric (type 2) synapses on spines indicated that their preferred location was opposite the asymmetric synapse on the head of the spine. Synaptic input to the necks of spines appears rare. 5. We conclude that most of the excitation provided by the geniculocortical afferent input to the heads of spines cannot be gated or vetoed by inhibition at the level of the spine.
1. We have studied in vivo the intracellular responses of neurones in cat visual cortex to electrical pulse stimulation of the cortical afferents and have developed a microcircuit that simulates much of the experimental data. 2. Inhibition and excitation are not separable events, because individual neurones are embedded in microcircuits that contribute strong population effects. Synchronous electrical activation of the cortex inevitably set in motion a sequence of excitation and inhibition in every neurone we recorded. The temporal form of this response depends on the cortical layer in which the neurone is located. Superficial layer (layers 2+3) pyramidal neurones show a more marked polysynaptic excitatory phase than the pyramids of the deep layers (layers 5+6). 3. Excitatory effects on pyramidal neurones, particularly the superficial layer pyramids, are in general not due to monosynaptic input from thalamus, but polysynaptic input from cortical pyramids. Since the thalamic input is transient it does not provide the major, sustained excitation arriving at any cortical neurone. Instead the intracortical excitatory connections provide the major component of the excitation. 4. The polysynaptic excitatory response would be sustained well after the stimulus, were it not for the suppressive effect of intracortical inhibition induced by the pulse stimulation. 5. Intracellular recording combined with ionophoresis of gamma-aminobutyric acid (GABA) agonists and antagonists showed that intracortical inhibition is mediated by GABAA and GABAB receptors. The GABAA component occurs in the early phase of the impulse response. It is reflected in the strong hyperpolarization that follows the excitatory response and lasts about 50 ms. The GABAB component occurs in the late phase of the response, and is reflected in a sustained hyperpolarization that lasts some 200-300 ms. Both components are seen in all cortical pyramidal neurones. However, the GABAA component appears more powerful in deep layer pyramids than superficial layer pyramids. 6. The microcircuit simulates with good fidelity the above data from experiments in vivo and provides a novel explantation for the apparent lack of significant inhibition during visual stimulation. The basic circuit may be common to all cortical areas studied and thus the microcircuit may be a 'canonical' microcircuit for neocortex.
The sites of infection by Caryospora bigenetica in Swiss-Webster mice (Mus musculus) were demonstrated after 7 routes of inoculation: oral, intraperitoneal, intravenous, intramuscular, subcutaneous, dermal, and intraocular. All mice exhibited clinical signs of dermal coccidiosis 9 days after inoculation regardless of the inoculation route. Signs included swelling of the facial tissue, footpads, and scrota (male mice). Developmental stages of the parasite were found in the muzzle, tongue, footpad, lumbar subcutaneous tissue, biceps femoris muscle, conjunctiva, and eye; the latter 3 sites represent new sites of development. The site of development of the parasite in the host tissue was independent of experimental inoculation route.
We have used computer simulation of a model neurone and in vitro intracellular recording to demonstrate that the adaptation of repetitive discharge in neocortical neurones can be explained by a fast potassium current whose inactivation is retarded by intracellular calcium. The maximum amplitude of this current determines whether the neurone will discharge in regular or burst mode.
Following unilateral 6-OHDA induced SN lesion, a transient period of contralateral rotation has been reported to precede the predominant ipsilateral circling. In order to clarify the nature of this initial contralateral rotation we examined the effect of the duration of recovery period after the lesion, on amphetamine-induced rotational behavior. Three days post lesion, most rats circled predominantly contralaterally to the lesion. Such contralateral rotation may result from either degeneration-induced breakdown of the DA pool, or lesion-induced increase of DA turnover in the spared neurons. A substantial degree of contralateral preference was still evident when amphetamine was administered for the first time 24 days after lesioning, indicating involvement of spared cells in the contralateral rotation. However, regardless of the duration of recovery (and irrespective of either lesion volume, amphetamine dose, or post-lesion motor exercise), amphetamine-induced rotation tended to become gradually more ipsilateral as the observation session progressed, and all rats circled ipsilaterally to the lesion in response to further amphetamine injections. These findings suggest that amphetamine has an irreversible effect on the post-lesion DA pool contributing to contralateral rotation.
A large battery of behavioral tests was administered to normal mice and to mice with varying degrees of otoconial agenesis due to genes affecting vestibular development. Many significant differences were found, but a factor analysis revealed that the variance on the 11 best tests could be accounted for in terms of two underlying variables. Factor I, the more important of the two, was associated with activity, habituation, and spontaneous alternation. Factor II appeared to represent a fear of new stimuli or situations. In both cases factor scores were highly related to the degree of otoconial deficiency. One subgroup of mice with severe otoconial agenesis displayed hyperactivity and a total absence of either habituation or spontaneous alternation. In these animals, brain and body development were stunted, and the reactions to amphetamine and physostigmine were opposite to those seen in normal mice. The results support the idea that the static organs contribute importantly to spatial orientation and suggest that early-onset vestibular defects can result in profound alterations of emotionality.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
This paper attempts to investigate taxonomic and phylogenetic relationships through an analysis of the distribution of mass within the brain. A multivariate analysis was performed on encephalization ratios for various divisions of the brain, employing volume measurements reported for 63 species by Stephan et al. [1970]. The ratios for each brain region were considered to lie along one of the dimensions of eight dimensional 'brain space', and distances between all species were calculated and employed in the determination of 'family trees'. It was assumed that modern species have, in many cases, brains representative of different stages of an evolutionary progression towards higher encephalization, and it was assumed that no 'backwards evolution' occurred. The family trees based on these data and assumptions were rigidly determined and do not represent mere opinion but, rather, inescapable conclusions if one accepts the premises. Most of the findings were in very good agreement with traditional or popular ideas, and this includes conclusions that tree shrews were ancestral to prosimians and that simians are derived from a tarsioid ancestor. Other findings, however, were just as strikingly deviant from current popular and expert thought. Present methods demanded, for example, that man must have a platyrrhine ancestry. While one may reject this particular conclusion it remains true that by present measures the human brain is much more like that of an American wooley or spider monkey than like that of either the chimpanzee or the gorilla.